Hexyl-chloro-m-cresol antiseptic



Patented May 4, 1943 Mich., assignors to Henry Ford Hospital, Detroit, Mich., a corporation of Michigan No Drawing. Original application November 16,

1939, Serial No. 304,706. Divided and this application September 6, 1941, Serial No. 409,902

1 Claim.

This invention relates to a new hydroxychloro-alkylbenzene compound known as 4- hexyl-G-chloro-meta-cresol, having remarkable antiseptic properties developed conjointly with our discovery of hexyl-dichloro-resorcinol described in application Serial No. 304,734, filed November 16, 1939, and application Serial No. 409,901, filed September 6, 1941. This application is a division of our earlier application Serial No. 304,706, filed November 16, 1939.

Like resorcinol, cresol has long been recognized for its disinfectant properties, and since both these substances are of the phenol series, the experimental development resulting in the present invention was somewhat similar to that of hexyl-dichloro-resorcinol in that it was desired to synthesize a compound combining cresol with the alkyl and halogen groups because of their known beneficial efiect upon the antiseptic power of phenolic compounds.

In the preparation of 4-hexyl-6-chloro-mcresol, 6-chloro-m-cresol, (2-chloro-5-hydroxy toluene Eastman) is used as the initial material. If the former substance is used 47 grams are placed in a flask fitted with a calcium chloride tube and 46 grams of caproyl chloride.

CHs-CI-Iz-CI-Iz-Cl-Iz-CI-Iz-COCl are added, the mixture being slowly heated until HCl gas begins to evolve. At this point the temperature is kept fairly constant until the reaction begins to be slower, when the temperature is gradually raised and kept near the boiling point for half an hour. If the commercial chloro-m-cresol is used, the interaction is between 1 mol. of this compound and 1 mol. of the caproylchloride. The resulting product is G-chloro-m-cresol caproylester as shown by the following chart:

CH3 I 1 OH C0 (CH2)-1CH3 After washing with boiling water, the ketone is dissolved in 3 parts of alcohol, and this solution is added to 6 volumes of H01 which has been heated in a three-neck flask fitted with a stirrer and a condenser.

Amalgamated zinc metal is added and the heating and stirring is continued until the ferric chloride reaction for ketone is negative.

crmonmom When the solution has cooled, the 6-chloro-4- hexyl-m-cresol is extracted with ether, the extract being washed with a weak sodium carbonate solution, dried with anhydrous sodium sulphate, and then distilled in high vacuum (below 1 mm. Hg) collecting the fraction which boils between -150 C. It is a clear liquid which crystallizes into a white mass in the cold.

6-chloro-4-hexyl-m-cresol is ideal as an antiseptic because it combines great strength with low toxicity and also retains remarkable killing power when greatly diluted. As with hexyl-dichloro-resorcinol, the effectiveness of the compound as an antiseptic is increased by the addition of small amounts of acid, sufficient to bring the pH down to 2 0r 3. The following table gives Highest dil. kills in 10 min. Tissue but not in a min. culture A B c 9 1 on;

S. aureus E. typhi 8000 06 8.

plus .30 Edi 10000 .045 2. ,000 5, 000 A Other acids, both organic and inorganic; will give a comparable increase in the efiectivefless of the substance, although some of these acids, notably tannic and hydrochloric, have abetter efiect than others. A pH value of 2 or 3 isrecommended because at this point there is a; markedincrease in the bactericidal properties with not only no increase but, in fact, a decrease of the tissue toxicity, which obviously should be kept as loW as possible. However, generally speaking, higher concentrations of acid will further increase the effectiveness and lower concentrations will decrease the effectiveness, as will buffering the solution, but exhaustive experiments indicate that the addition of acids, as above described, is broadly applicable to all carbocyclic antiseptics.

We claim:

A new compound having the formula FRANK W. HARTMAN. VICTOR SCHELLING. 

